crossing96/oncoscreening huggingface dataset:
Micropapillary urothelial carcinoma of the urinary bladder: a clinicopathological analysis of 72 cases.	AIM: Micropapillary carcinoma (MPC) of the bladder is an aggressive variant of urothelial carcinoma (UC). It is unknown if any amount of a micropapillary component justifies the diagnosis of MPC. It is also unknown if surface MPC also has aggressive potential. METHODS: We studied 72 patients with UC with a micropapillary component in transurethral resections of bladder (TURB) diagnosed between 1998 and 2008. Fifty-seven patients were treated with radical cystectomy. Tumours were classified according to pathological (pT) stage and percentage of MPC (≤ 10%, 10-49%, 50-100%). This was correlated with clinical data and follow up. Significant factors in univariate analysis were entered into a multivariate analysis. RESULTS: In the TURB specimens, 12 had pTa, 33 pT1 and 27 pT2 tumours with 23% also displaying urothelial carcinoma in situ (CIS). On cystectomy, the MPC component was upstaged in 79% of cases. Twenty-five (35%) patients had metastases at presentation or nodal metastases at cystectomy and 27 patients (38%) died of disease. Mean survival was 17.8 months. Of 12 pTa MPC cases, eight were treated with cystectomy, all displaying invasive carcinoma including five (62%) with pT2-pT4 disease. Three (25%) of these patients died of disease. Seven patients had a MPC component of <10% all of whom had cystectomy. Six of these had invasive carcinoma including two (33%) with pT2-pT4 disease. One (15%) of these patients died of disease. On univariate analysis, the proportion of the MPC component on TURB and pathological stage predicted disease specific survival (p=0.01 and 0.004, respectively), while presence of CIS predicted recurrence (p=0.03). On multivariate analysis, CIS predicted recurrence (p=0.003); however, the proportion of MPC in TURB did not remain significant in predicting disease specific survival. The pathological stage of MPC remained significant in predicting disease specific survival (p=0.04). CONCLUSIONS: Any amount of MPC, even <10% is significant in urothelial carcinoma and should be reported. Surface MPC is associated with invasive carcinoma in most cases which can be high stage. Adequate sampling to include detrusor muscle is crucial in these cases. Associated CIS is important to be recognised and reported as this also impacts on clinical outcome.	bladder
GSTT1: a marker of the aggressiveness of bladder cancer.	INTRODUCTION: Glutathione S-transferases have been implicated in the development of bladder cancer (BC). We investigated the genotype and expression of glutathione S-transferase-mu (GSTM1) and glutathione S-transferase-theta (GSTT1) in BC tissue specimens. MATERIALS AND METHODS: Tumor samples and matched normal mucosae were obtained from 34 patients. Genomic DNA was used to analyze GSTM1 and GSTT1 genotypes using multiplex polymerase chain reaction. GSTM1 and GSTT1 mRNA levels were measured using real-time reverse transcriptase polymerase chain reaction. RESULTS: GSTM1 mRNA expression was lower in tumor tissues than in matched normal bladder mucosae, whereas GSTT1 mRNA expression was significantly higher. GSTT1 mRNA expression was higher in muscle-invasive BC and high-grade cancers than in non-muscle-invasive BC and lower-grade tumors. CONCLUSIONS: GSTT1 is correlated with characteristics of aggressive BC. GSTT1 may play an important role in tumorigenesis and disease progression in patients with BC.	bladder
Determining factors for hospital discharge status after radical cystectomy in a large contemporary cohort.	PURPOSE: We describe hospital discharge status in patients after radical cystectomy for bladder cancer. We determined factors affecting discharge status. MATERIALS AND METHODS: The 445 patients underwent radical cystectomy for urothelial carcinoma from January 2004 to December 2007. Patients were grouped by hospital discharge status into 1 of 4 groups, including home under self-care without services, home with home health services, subacute, rehabilitation or skilled nursing facility, or hospice/in-hospital mortality. We compared clinical, perioperative and pathological variables in these groups. We also examined the association of discharge status with the hospital readmission rate and 90-day mortality. RESULTS: Of the 440 patients 250 (56.8%), 145 (32.9%), 39 (8.9%) and 6 (1.4%) were in the home without services, home with services, facility and mortality groups, respectively. On multivariate analysis older age, lower preoperative albumin, unmarried status and higher Charlson comorbidity index were predictors of discharge home with services while older age, poor preoperative exercise tolerance and longer hospital stay predicted discharge to a facility. Patients in the facility group were more likely to die within 90 days of surgery than those who returned home independently or with services. There was no difference in the likelihood of rehospitalization. CONCLUSIONS: Sociodemographic factors, preoperative performance status, and comorbidities and perioperative factors contribute to the discharge decision after radical cystectomy. Some subgroups can be predicted to have increased postoperative care needs and may be appropriate targets for disposition planning preoperatively.	bladder
Extranodal extension in node-positive bladder cancer: the continuing controversy.	OBJECTIVE: • To examine whether extranodal extension (ENE) has an impact on the outcome of node-positive patients who underwent radical cystectomy for bladder cancer. PATIENTS AND METHODS: • Of 543 consecutive patients who underwent radical cystectomy for urothelial carcinoma of the bladder between 1990 and 2007, 112 patients with lymph node metastasis detected on histological examination were evaluated with regard to recurrence-free survival (RFS) and disease-specific survival (DSS) based on ENE status. RESULTS: • The overall 5-year RFS and DSS rates were 22.3% and 33.8%, respectively. ENE was observed in 41 (36.6%) of the 112 patients. • The presence of ENE was associated with advanced pathological nodal status (P= 0.004), more positive lymph nodes (P= 0.006), and higher lymph node density (P < 0.001). • The incidence of positive ENE increased with large positive lymph node diameter (P < 0.001). • Multivariate analysis showed that lymph node density (hazard ratio (HR) = 2.39, 95% CI 1.09-5.24, P= 0.029; and HR = 3.13, 1.43-6.84, P= 0.004) and use of adjuvant chemotherapy (HR = 1.80, 1.02-3.20, P= 0.041; and HR = 2.07, 1.13-3.79, P= 0.018) were significant predictors of RFS and DSS, respectively. • After adjustment for other prognostic factors, ENE was not significantly related to RFS (P= 0.825) and DSS (P= 0.961) by multivariate analysis. CONCLUSIONS: • The presence of ENE was not an independent prognostic factor in node-positive patients after radical cystectomy for bladder cancer. • Additional prospective studies are needed to determine the independent prognostic role of ENE.	bladder
Robotic extended pelvic lymphadenectomy for bladder cancer with increased nodal yield.	STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? The standard of care for invasive bladder cancer is open radical cystectomy with the extent of pelvic lymph node dissection impacting oncological outcomes. Scepticism remains regarding whether an adequate node dissection can be performed in minimally-invasive fashion as previously reported nodal yields of laparoscopic or robotic lymphadenectomy are well below those reported with open surgery. This study demonstrates that extended pelvic lymphadenectomy can be performed robotically with equivalent nodal yields to open series from centres of excellence. OBJECTIVE: To report our initial experience with robot-assisted extended pelvic lymph node dissection (ePLND) using a standardized open template. PATIENTS AND METHODS: In total, 15 consecutive patients underwent robotic radical cystectomy at a single center by a single surgeon using a standard dissection template. Operating time, time to perform ePLND, pathological stage, estimated blood loss, length of hospital stay, number of nodes obtained and nodal positivity were assessed. Postoperative complications and re-admissions were reviewed. RESULTS: The mean (range) age and body mass index was 66 (46-87) years and 29 (22-43) kg/m2, respectively. The mean (range) operating time and ePLND time was 423 (300-506) min and 107 (66-160) min. Mean (range) estimated blood loss was 160 (50-500) mL. The mean (range) and median length of hospital stay were 3.4 (3-7) days and 3 days, respectively. The mean (range) nodal yield was 41.8 (18-67) nodes, with greater than 25 nodes in 13 patients. Three patients were found to have nodal positivity. Of the fifteen patients, four received neoadjuvant chemotherapy. Two patients were re-admitted for postoperative complications within 30 days. There were no complications directly resulting from the ePLND. CONCLUSIONS: Robot-assisted ePLND at the time of cystectomy can be safely and effectively performed on the robotic platform with comparable nodal yields to open series at centers of excellence for cystectomy. Nodal yields are likely to comprise a factor related to the effort of the surgeon, and not the method by which the lymphadenectomy is performed.	bladder
The uptake of paclitaxel and docetaxel into ex vivo porcine bladder tissue from polymeric micelle formulations.	Superficial bladder cancer occurs in the urothelial layer of the bladder and is usually treated by transurethral resection and chemotherapy. Although the bladder is well suited for intravesical chemotherapy, effective drug delivery is restricted by urine dilution and poor drug uptake by bladder tissues during a 2 h instillation. In this study, freshly excised pig bladder sections were mounted on Franz diffusion cells and treated with anticancer drugs paclitaxel (PTX) and docetaxel (DTX) formulated in diblock copolymer (methoxy poly(ethylene glycol)-block-poly (D,L-lactic acid) (MePEG-PDLLA) and methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-PCL) nanoparticles for 2 h. The bladder sections were then frozen, cryosectioned (60-μm sections) and the amount of (3)H drug taken up into each section was determined using liquid scintillation counting. Tissue concentration versus tissue depth profiles were obtained for all drug formulations and drug exposure obtained from area-under-the-curve (AUC) calculations. PTX or DTX loaded in MePEG-PDLLA micelles produced significantly higher urothelial tissue levels and greater bladder wall exposures compared to their commercial formulations, Cremophor EL/ethanol (PTX) or Tween 80 (DTX). The results of this study support the use of diblock copolymer micellar PTX or DTX formulations as they allow for improved drug penetration of bladder tissues compared to commercial formulations for taxane delivery to superficial bladder tumors.	bladder
Parity, early menopause and the incidence of bladder cancer in women: a case-control study and meta-analysis.	INTRODUCTION: Incidence rates of bladder cancer are notably higher in men than in women. While there is evidence that reproductive and hormonal risk factors may influence risk of bladder cancer, data are inconclusive. MATERIALS AND METHODS: We examined reproductive, menstrual and hormonal use history in our population-based case-control study of bladder cancer in New Hampshire (NH), USA (n=207 women cases and n=463 women controls). Additionally, we performed a meta-analysis of the published literature. We used unconditional logistic regression analysis to compute adjusted odds ratios associated with each risk factor in the NH study. We combined these estimates with those from the published literature using inverse variance effects models. RESULTS: In the NH study, a slightly decreased odds ratio was found among women who had ever had a birth compared to nulliparous women and an elevated odds ratio among women who underwent surgical menopause (bilateral oophorectomy), especially at an early age. No overall associations were found with oral contraceptive use or hormone replacement therapy. These findings were generally in agreement with the meta-analytic results for which the combined relative risk (RR) estimate was reduced among ever parous women (combined RR estimate for ever parous versus nulliparous=0.66, 95% confidence intervals [95% CI] 0.55-0.79) and elevated among those undergoing an early menopause (combined RR estimate for early versus late menopause=1.59, 95% CI 1.31-1.92). No consistent risk was observed for the other factors. DISCUSSION: Some reproductive and menstrual factors appear to be related to the incidence of bladder cancer among women; but whether effects are due to female hormones is uncertain.	bladder
Environmental tobacco smoke in relation to bladder cancer risk--the Shanghai bladder cancer study [corrected].	BACKGROUND: Environmental tobacco smoke (ETS) contains tobacco carcinogens. Hepatic cytochrome P450 (CYP) 1A2 and N-acetyltransferase (NAT2) are important isoenzymes in activation and detoxification, respectively, of tobacco carcinogens. Data on ETS and bladder cancer risk are sparse. METHODS: We examined the effects of ETS alone and combined with NAT2/CYP1A2 on bladder cancer risk among lifelong-nonsmokers in a case-control study involving 195 patients and 261 controls in Shanghai, China. A comprehensive history of ETS exposure was determined through in-person interviews while CYP1A2 and NAT2 phenotypes by a caffeine-based urinary assay. RESULTS: ETS exposure was related to an overall statistically nonsignificant 38% increased bladder cancer risk. The risk increased with increasing number of cigarettes smoked by household members or number of hours per day at workplace where coworkers smoked. Compared with no ETS exposure, subjects living with smoking parents during childhood had an OR of 2.43 (95% CI = 0.99-5.96) for bladder cancer. When all ETS sources were combined, the risk increased with increasing total ETS score (P(trend) = 0.03). The OR for high versus nil ETS exposure was 3.00 (95% CI = 1.24-7.26). The increased risk with ETS was mainly seen among individuals possessing a CYP1A2 high efficiency and/or a NAT2 slow acetylation phenotype (P(trend) = 0.04). CONCLUSIONS: ETS was associated with an increased bladder cancer risk for lifelong-nonsmokers. The association was stronger for people possessing the at-risk phenotypes of CYP1A2 and/or NAT2. IMPACT: Reducing exposure to ETS for children and genetically more susceptible individuals could be more effective for bladder cancer prevention.	bladder
High-magnification vascular imaging to reject false-positive sites in situ during Hexvix® fluorescence cystoscopy.	Fluorescence imaging for detection of non-muscle-invasive bladder cancer is based on the selective production and accumulation of fluorescing porphyrins-mainly, protoporphyrin IX-in cancerous tissues after the instillation of Hexvix®. Although the sensitivity of this procedure is very good, its specificity is somewhat limited due to fluorescence false-positive sites. Consequently, magnification cystoscopy has been investigated in order to discriminate false from true fluorescence positive findings. Both white-light and fluorescence modes are possible with the magnification cystoscope, allowing observation of the bladder wall with magnification ranging between 30× for standard observation and 650×. The optical zooming setup allows adjusting the magnification continuously in situ. In the high-magnification (HM) regime, the smallest diameter of the field of view is 600 microns and the resolution is 2.5 microns when in contact with the bladder wall. With this cystoscope, we characterized the superficial vascularization of the fluorescing sites in order to discriminate cancerous from noncancerous tissues. This procedure allowed us to establish a classification based on observed vascular patterns. Seventy-two patients subject to Hexvix® fluorescence cystoscopy were included in the study. Comparison of HM cystoscopy classification with histopathology results confirmed 32∕33 (97%) cancerous biopsies and rejected 17∕20 (85%) noncancerous lesions.	bladder
Short interfering RNA directed against Slug blocks tumor growth, metastasis formation, and vascular leakage in bladder cancer.	In a previous study, we have identified Slug as selectively overexpressed in the highly invasive bladder cancer cells. Furthermore, Slug overexpression was correlated with metastasis in bladder cancer tissues. Here, we investigated the role and underlying mechanism of Slug in the process of growth, invasion and metastasis formation, and vascular leakage in a bladder cancer cell line T24. We knocked down in a bladder cancer cell line T24 by Slug siRNA, and the effects on invasion, metastasis, and proliferation were evaluated in vitro. A pseudometastatic model of bladder cancer in severe combined immunodeficient mice was used to assess the effects of Slug silencing on metastasis and angiogenesis development. Slug-specific siRNA in T24 cells led to a significant decrease in invasiveness and metastasis, proliferation rates, and angiogenesis in vitro. Slug-specific siRNA induced strong changes in cell invasiveness mainly through a mechanism of up-regulation of epithelial markers E-cadherin expression. Interestingly, E-cadherin-specific siRNA attenuated Slug siRNA-induced Matrigel invasion. Moreover, Slug-specific siRNA induced strong changes in microvessel counts in angiogenesis mainly through decreased activity of MMP-2, but not through cadherin expression and decreased activity of MMP-9. Restoration of MMP-2 expression in the Slug-silenced T24 cells resulted in an increased cell angiogenesis. Moreover, Slug-specific siRNA significantly reduced tumor growth by approximately 60% and inhibited metastasis and angiogenesis in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and a decreased expression of MMP-2 in tumor tissues. These data suggest that Slug regulates tumor growth, invasion and metastasis, and angiogenesis through E-cadherrin and MMPS passway. Blocking Slug signaling in bladder cancer may represent a novel strategy in the future to reduce metastatic disease burden in bladder cancer patients.	bladder
Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men.	We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different ethnicity are required to confirm our findings.	bladder
Organotypic and 3D reconstructed cultures of the human bladder and urinary tract.	Three-dimensional organotypic cultures of human urinary tract tissue have been established as intact and reconstituted tissues, with the latter generated by combining cultured normal human urothelial (NHU) cells with an appropriate stroma. Organoids may be maintained at an air-liquid interface in static culture for periods of up to 20 weeks, with analysis by immunohistology for expression of urothelial differentiation-associated markers providing a qualitative, but objective assessment criterion. Where reconstructed using bladder cancer cell lines, the resultant organoids recapitulate the invasive characteristics of the originating tumour, but the need to use authenticated cell line stocks is emphasised. The organoid approach represents an important tool for investigating urothelial-stromal cell interactions during homeostasis and disease, and for testing bladder tissue engineering and reconstructive strategies. Potential future developments of the technique are discussed and include genetic manipulation of the urothelial cells to generate disease models and incorporation of biomaterial scaffolds to support artificial stroma development.	bladder
Bladder metastasis of malignant melanoma: a case report and review of literature.	Metastatic malignant melanoma of the bladder is extremely rare in clinical practice with less than 10 cases reported in the last 30 years in the English literature. We report a case of malignant melanoma metastasis into the bladder, and review of the pertinent literature. A 60-year-old woman with a history of malignant melanoma in the distal phalanx on the right middle finger, excised 8 years ago presented with gross hematuria and weight loss. She underwent cystoscopy and complete transurethral resection of the bladder tumor. Pathological examination showed metastatic malignant melanoma of the bladder mucosa. The patient eventually died 7 months after transurethral resection.	bladder